Novel Pyrazole and Indazole Derivatives: Synthesis and Evaluation of Their Anti‐Proliferative and Anti‐Angiogenic Activities

Abstract

The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values of 1.5 ± 0.4 µM and 5.6 ± 2.5 µM, respectively, against MCF-7 cells. In addition, the indazole derivative 16 was assessed as a competent inhibitor of endothelial tube formation at 30 µM.

Antiproliferative and antibacterial activity of 3-arylbenzo[<em>g</em>]indazoles functionalized with nitro and amino groups at position 6

“…Indazoles are benzo-fused pyrazoles for which a broad range of biological properties have been described, including antiproliferative and antibacterial activities [2,3]. These fused tricyclic pyrazole derivatives are characterized by their conformational restriction.…”

Assessment of the Antitumor Potentiality of Newly Designed Steroid Derivatives: Pre-Clinical Study

“…Treatment of HCC group with compounds 5, 4 or 3 yields significant depletion in serum AFP, ENG, LCN-2 and HSP-70 levels when compared with HCC group. Several types of steroids have been modified to be cytotoxic and cytostatic (antiproliferative) anticancer candidates (Tzanetou et al, 2012). Also, many steroids were among the first molecules identified as antiangiogenic agents (Labbozzetta et al, 2009).…”

Novel conformationally constrained pyrazole derivatives as potential anti-cancer agents

“…To extend the use of ketone substrates, the N-benzylated indolone 21 was selected as starting material for the synthesis of novel indazole derivatives using a modification of a procedure published previously by our group [12]. Briefly, indolone in the presence of lithium hexamethyldisilazane (LHMDS) base under anhydrous conditions provided the corresponding anion, which was subsequently condensed with p-anisoyl chloride or 3-chlorobenzothiophene-2-carbonyl chloride to yield the 1,3-diketone derivatives.…”

“…The synthesis of anti-cancer pyrazoles was recently reviewed by Kumari et al [11], indicating that several analogues are in preclinical or initial-phase clinical trials. In the course of our longstanding interest concerning the development of novel bioactive heterocycles [12,13], we have designed and synthesized a sequence of novel bioactive molecules containing the pyrazole residue [12][13][14]. Herein, we present the outcome of our vision to design and synthesize several novel molecules containing the pyrazole structural backbone fused with commercially available constrained ketone substrates.…”